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Construction of high-yield substance-producing microorganisms by using different sugars

Research Project

Project/Area Number 19H02526
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 27040:Biofunction and bioprocess engineering-related
Research InstitutionKobe University

Principal Investigator

Tsutomu Tanaka  神戸大学, 工学研究科, 准教授 (90436551)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Keywords代謝工学 / バイオリファイナリー
Outline of Research at the Start

本研究では「増殖 or 生産」というジレンマを脱却して「増殖 and 生産」という新しい方法論を提案する。解糖系とTCA回路を完全に切り離し、さらに糖を使い分けることで、微生物に最初から増殖に違う経路を使ってもらう技術を開発する。基盤微生物を構築しPEPおよびアセチルCoAを前駆体とする有用化合物(ムコン酸・メバロン酸)の炭素収率を劇的に向上させる。

Outline of Final Research Achievements

In this study, we developed a new metabolic engineering technology called PMPE (Parallel Metabolic Pathway Engineering). We used glucose and xylose as carbon sources for the production of target substances and cell growth, respectively, and designed the system so that the carbon derived from each sugar does not intersect within the metabolic system. After further examination of the culture medium and optimization of pH, MA was produced at 4.26 g/L after 80 hours of incubation, and the MA yield relative to consumed glucose reached 0.31 g/g after 80 hours of incubation. This yield was the highest in the world for MA production in batch operation, indicating that PMPE is an effective strategy.

Academic Significance and Societal Importance of the Research Achievements

低炭素社会の実現には、いかに炭素を効率よく使うか、つまり収率の向上が大きな鍵となる。しかし、微生物は投入した炭素源を物質生産ではなく菌体増殖の方へと流してしまう。そこで本研究では、Parallel Metabolic Pathway Engineering (PMPE)という新しい手法を開発した。本技術は、収率の向上のみならず、使える炭素源の種類を拡張させる点でも低炭素化に大きく貢献している。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (29 results)

All 2022 2021 2020 2019 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (22 results) (of which Int'l Joint Research: 14 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] G6P-capturing molecules in the periplasm of Escherichia coli accelerate the shikimate pathway2022

    • Author(s)
      Fujiwara, R., Nakano, M., Hirata, Y., Otomo, C., Nonaka, D., Kawada, S., Nakazawa, H., Umetsu, M., Shirai, T., Noda, S.*, Tanaka, T.*, Kondo, A.
    • Journal Title

      Metabolic Engineering

      Volume: 72 Pages: 68-81

    • DOI

      10.1016/j.ymben.2022.03.002

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Metabolic engineering of 1,2-propanediol production from cellobiose using beta-glucosidase-expressing E. coli2021

    • Author(s)
      Nonaka Daisuke、Fujiwara Ryosuke、Hirata Yuuki、Tanaka Tsutomu、Kondo Akihiko
    • Journal Title

      Bioresource Technology

      Volume: 329 Pages: 124858-124858

    • DOI

      10.1016/j.biortech.2021.124858

    • NAID

      120007026334

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Metabolic Engineering of Shikimic Acid-Producing Corynebacterium glutamicum From Glucose and Cellobiose Retaining Its Phosphotransferase System Function and Pyruvate Kinase Activities2020

    • Author(s)
      Sato Naoki、Kishida Mayumi、Nakano Mariko、Hirata Yuuki、Tanaka Tsutomu
    • Journal Title

      Frontiers in Bioengineering and Biotechnology

      Volume: 8 Pages: 569406-569406

    • DOI

      10.3389/fbioe.2020.569406

    • NAID

      120006894009

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metabolic engineering of E. coli for improving mevalonate production to promote NADPH regeneration and enhance acetyl-CoA supply2020

    • Author(s)
      Satowa Daichi、Fujiwara Ryosuke、Uchio Shogo、Nakano Mariko、Otomo Chisako、Hirata Yuuki、Matsumoto Takuya、Noda Shuhei、Tanaka Tsutomu、Kondo Akihiko
    • Journal Title

      Biotechnology and Bioengineering

      Volume: - Issue: 7 Pages: 2153-2164

    • DOI

      10.1002/bit.27350

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose?xylose co-substrate2020

    • Author(s)
      Fujiwara Ryosuke、Noda Shuhei、Tanaka Tsutomu、Kondo Akihiko
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 279-291

    • DOI

      10.1038/s41467-019-14024-1

    • NAID

      120006818769

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 大腸菌を用いたカフェ酸生産技術の開発2021

    • Author(s)
      寒河江 康介、野中 大輔、藤原 良介、田中 勉、近藤 昭彦
    • Organizer
      化学工学会 第52回秋季大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] コリネ菌を用いたメチオニン生産技術の開発2021

    • Author(s)
      盛尾 美和、田中 勉、近藤 昭彦
    • Organizer
      化学工学会 第52回秋季大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 油性酵母を宿主とした三酢酸ラクトン生産技術の開発2021

    • Author(s)
      松岡 宥汰、藤江 直史、田中 勉、近藤 昭彦
    • Organizer
      化学工学会 第52回秋季大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Production of 4-hydroxybenzoic acid from glucose using Corynebacterium glutamicum2021

    • Author(s)
      Misa Doke, Miwa Morio, Tsutomu Tanaka, Akihiko Kondo
    • Organizer
      The 26th Symposium of Young Asian Biological Engineers’ Community
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] コリネ菌を用いたグルコースからの 4-ヒドロキシ安息香酸生産技術の開発2021

    • Author(s)
      道家 美紗、盛尾 美和、田中 勉、近藤 昭彦
    • Organizer
      第73回日本生物工学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Metabolic engineering of Escherichia coli for caffeic acid production2021

    • Author(s)
      Kosuke Sakae, Daisuke Nonaka, Ryosuke Fujiwara, Tsutomu Tanaka, and Akihiko Kondo
    • Organizer
      The 26th Symposium of Young Asian Biological Engineers’ Community
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Aerobic production of 1,2-propanediol in engineered Escherichia coli by dividing metabolic pathway2021

    • Author(s)
      Daisuke Nonaka, Ryosuke Fujiwara, Tsutomu Tanaka, and Akihiko Kondo
    • Organizer
      Metabolic Engineering 14
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 代謝経路の分断による 1,2-プロパンジオールの好気発酵生産技術の開発2021

    • Author(s)
      野中 大輔、藤原 良介、田中 勉、近藤 昭彦
    • Organizer
      第73回日本生物工学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Vanillin production from glucose in engineered Schizosaccharomyces pombe2021

    • Author(s)
      Wakana Kawamura, Naofumi Fujie, Tsutomu Tanaka, Akihiko KondoWakana Kawamura, Naofumi Fujie, Tsutomu Tanaka, Akihiko Kondo
    • Organizer
      The 26th Symposium of Young Asian Biological Engineers’ Community
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Metabolic engineering of Corynebacterium glutamicum for l-methionine production2021

    • Author(s)
      Metabolic engineering of Corynebacterium glutamicum for l-methionine production
    • Organizer
      The 26th Symposium of Young Asian Biological Engineers’ Community
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Metabolic engineering of Schizosaccharomyces pombe for itaconic acid production2021

    • Author(s)
      Naofumi Fujie, Miki Ito, Tsutomu Tanaka, Akihiko Kondo
    • Organizer
      The 26th Symposium of Young Asian Biological Engineers’ Community
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dividing metabolic pathway in Escherichia coli for high-yield 1,2-propanediol production under aerobic condition2021

    • Author(s)
      Daisuke Nonaka, Ryosuke Fujiwara, Tsutomu Tanaka, and Akihiko Kondo
    • Organizer
      The 26th Symposium of Young Asian Biological Engineers’ Community
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Triacetic acid lactone production from glucose using Yarrowia lipolytica2021

    • Author(s)
      Yuta Matsuoka, Naofumi Fujie, Tsutomu Tanaka, and Akihiko Kondo
    • Organizer
      The 26th Symposium of Young Asian Biological Engineers’ Community
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 大腸菌の代謝改変による1,2-プロパンジオール生産技術の開発2020

    • Author(s)
      野中 大輔・藤原 良介・ 田中 勉・ 近藤 昭彦
    • Organizer
      化学工学会第86年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Parallel Metabolic Pathway Engineeringを用いた大腸菌による高収率物質生産2019

    • Author(s)
      藤原良介, 野田修平, 田中 勉, 近藤昭彦
    • Organizer
      酵素工学研究会第82回講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] コリネ菌におけるシキミ酸経路の強化2019

    • Author(s)
      佐藤直樹, 田中 勉, 近藤昭彦
    • Organizer
      酵素工学研究会第82回講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Production of shikimic acid using metabolically engineered Corynebacterium glutamicum2019

    • Author(s)
      Naoki SATO, Rena MATSUURA, Tsutomu TANAKA, Akihiko KONDO
    • Organizer
      18th Asian Pacific Confederation of Chemical Engineering Congress (APCChE 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Metabolic engineering to improve 1,5-diaminopentane production from cellobiose using BGL-secreting Corynebacterium glutamicum2019

    • Author(s)
      Tanaka, T., Kondo, A.
    • Organizer
      14th International symposium on Biocatalysis and Biotransformations (Biotrans 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] High yield bioproduction of shikimate pathway derivatives by"Parallel Metabolic Design"2019

    • Author(s)
      Naoki SATO, Rena MATSUURA, Tsutomu TANAKA, Akihiko KONDO
    • Organizer
      14th International symposium on Biocatalysis and Biotransformations (Biotrans 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] High yield bioproduction of shikimate pathway derivatives by"Parallel Metabolic Design"2019

    • Author(s)
      Fujiwara Ryosuke、Noda Shuhei、Tanaka Tsutomu、Kondo Akihiko
    • Organizer
      14th International symposium on Biocatalysis and Biotransformations (Biotrans 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Enhancing 3-hydroxypropionic acid production in combination with cell surface display and metabolic engineering of S. pombe2019

    • Author(s)
      Tanaka, T., Kondo, A.
    • Organizer
      Symposium on Biotechnology for Fuels and Chemicals (SBFC)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] High yield production of muconic acid from glucose by supplementing the carbon source from xylose for cell growth.2019

    • Author(s)
      Fujiwara Ryosuke、Noda Shuhei、Tanaka Tsutomu、Kondo Akihiko
    • Organizer
      Symposium on Biotechnology for Fuels and Chemicals (SBFC)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 微生物に糖を目的別に使い分けさせる新技術でポリマー原料の生産性向上に成功

    • URL

      https://www.kobe-u.ac.jp/research_at_kobe/NEWS/news/2020_01_14_02.html

    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 糖代謝経路が改変された微生物2019

    • Inventor(s)
      田中勉、野田修平、藤原良介
    • Industrial Property Rights Holder
      田中勉、野田修平、藤原良介
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-089294
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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